Involvement of the fibroblast growth factor system in adaptive and chemokine-induced arteriogenesis

Fibroblast growth factors (FGFs) have been applied in a variety of therapeutic and experimental studies to improve collateral blood flow. However, the pathophysiological role and the temporospatial expression of the FGFs and their receptors during arteriogenesis have never been elucidated in vivo. Here, we report that collateral artery growth in its early phase is associated with an increased expression of FGF receptor-1 (FGFR-1) and syndecan-4 on mRNA and protein levels as well as with an increased kinase activity of FGFR-1 in a rabbit model of arteriogenesis. However, the mRNA levels of FGF-1 and -2 remained constant. Our data suggest that these growth factors are supplied by endothelial attracted monocytes that, in turn, produce and deliver the FGFs to growing collateral arteries. Monocyte chemoattractant protein-1-stimulated arteriogenesis was strongly reduced in rabbits by application of the FGF inhibitor polyanetholesulfonic acid, indicating that the monocyte-related arteriogenesis (as well as the unstimulated adaptation proper) is promoted by FGFs. In summary, this study shows that arteriogenesis is associated with an increased expression of the FGFRs at the site of the vessel, whereas the growth-promoting ligands are supplied by monocytes in a paracrine way

What can ecological data tell us about reasons for divergence in health status between west central Scotland and other regions of post-industrial Europe

<p>Background: The link between the effects of de-industrialization (unemployment, poverty) and population health is well understood. Post-industrial decline has, therefore, been cited as an underlying cause of high mortality in Scotland's most de-industrialized region. However, previous research showed other comparably de-industrialized regions in Europe to have better and faster improving health (with, in many cases, a widening gap evident from the early to mid-1980s).</p> <p>Objectives: To explore whether ecological data can provide insights into reasons behind the poorer, and more slowly improving, health status of West Central Scotland (WCS) compared with other European regions that have experienced similar histories of post-industrial decline. Specifically, this study asked: (1) could WCS's poorer health status be explained purely in terms of socio-economic factors (poverty, deprivation etc.)? and (2) could comparisons with other health determinant information identify important differences between WCS and other regions? These aims were explored alongside other research examining the historical, economic and political context in WCS compared with other de-industrialized regions.</p> <p>Study design and methods: A range of ecological data, derived from surveys and routine administrative sources, were collected and analysed for WCS and 11 other post-industrial regions. Analyses were underpinned by the collection and analysis of more detailed data for four particular regions of interest. In addition, the project drew on accompanying literature-based research, analysing important contextual factors in de-industrialized regions, including histories of economic and welfare policies, and national and regional responses to de-industrialization.</p> <p>Results: The poorer health status of WCS cannot be explained in terms of absolute measures of poverty and deprivation. However, compared with other post-industrial regions in Mainland Europe, the region is distinguished by having wider income inequalities and associated social characteristics (e.g. more single adults, lone parent households, higher rates of teenage pregnancy). Some of these distinguishing features are shared by other UK post-industrial regions which experienced the same economic history as WCS.</p> Conclusion From the collection of data and supporting analyses of important contextual factors, one can argue that poor health in WCS can be attributed to three layers of causation: the effects of de-industrialization (which have impacted on health in all post-industrial regions); the impact of ‘neoliberal’ UK economic policies, resulting in wider inequalities in WCS and the other UK regions; and an as-yet-unexplained (but under investigation) set of factors that cause WCS to experience worse health outcomes than similar regions within the UK